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A rotary mechanism for allostery in bacterial hybrid malic enzymes

DOI: 10.1038/s41467-021-21528-2 DOI Help

Authors: Christopher John Harding (University of Birmingham) , Ian Thomas Cadby (University of Birmingham) , Patrick Joseph Moynihan (University of Birmingham) , Andrew Lee Lovering (University of Birmingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: February 2021
Diamond Proposal Number(s): 14692

Open Access Open Access

Abstract: Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux. Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA, a molecular indicator of the metabolic state of the cell. Here we solve the structure of a MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA) domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic enzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scale rearrangement that rotates the catalytic subunits 70° between the two states, identifying MaeB as a new model enzyme for the study of ligand-induced conformational change. Our work provides the mechanistic basis for metabolic control of hybrid malic enzymes, and identifies inhibition-insensitive variants that may find utility in synthetic biology.

Journal Keywords: Enzyme mechanisms; Oxidoreductases; X-ray crystallography

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography


Discipline Tags:

Catalysis Life Sciences & Biotech Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)